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Molecularly targeted photodynamic therapy targeting cancer related mRNA G-quadruplex

Research Project

Project/Area Number 16K14042
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Bio-related chemistry
Research InstitutionKonan University

Principal Investigator

MIYOSHI Daisuke  甲南大学, フロンティアサイエンス学部, 教授 (50388758)

Co-Investigator(Kenkyū-buntansha) 川内 敬子  甲南大学, フロンティアサイエンス学部, 講師 (40434138)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords四重らせん構造 / RNA / NRAS / がん / 光線力学療法 / 分子標的型 / フタロシアニン / mRNA / リガンド / RAS / 活性酸素 / 分子標的
Outline of Final Research Achievements

Ras signaling pathways contributes to aggressive phenotypes of cancer cells. The Ras-targeted therapies for cancer therefore has been recognized to be absolutely effective. On the other hand, it is well known that drug developments targeting Ras is very difficult due to structural feature of Ras protein.
In this project, we found that expression of N-Ras was able to be controlled by photo-irradiation with an anionic phthalocyanine, ZnAPC, targeting NRAS mRNA, which forms a G-quadruplex at its 5' UTR region. It was shown that ZnAPC bound G-quadruplex-forming oligonucleotide derived from NRAS mRNA and cleaved it upon photo-irradiation. Consistent with these results, the combination of photo-irradiation and ZnAPC decreased N-Ras expression and drastically reduced cell viability of cancer cells, MCF-7 cells. These results demonstrate that ZnAPC is prominent for a molecular-targeted photodynamic cancer therapy.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (46 results)

All 2018 2017 2016 Other

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 5 results,  Acknowledgement Compliant: 3 results) Presentation (36 results) (of which Int'l Joint Research: 14 results,  Invited: 13 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Unexpected Position-Dependent Effects of Ribose G-Quartets in G-Quadruplexes2017

    • Author(s)
      Zhou Jun、Amrane Samir、Rosu Frederic、Salgado Gilmar F.、Bian Yunqiang、Tateishi-Karimata Hisae、Largy Eric、Korkut Dursun Nizam、Bourdoncle Anne、Miyoshi Daisuke、Zhang Jian、Ju Huangxian、Wang Wei、Sugimoto Naoki、Gabelica Valerie、Mergny Jean-Louis
    • Journal Title

      Journal of the American Chemical Society

      Volume: 139 Issue: 23 Pages: 7768-7779

    • DOI

      10.1021/jacs.7b00648

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Highly Sensitive Telomerase Assay Insusceptible to Telomerase and Polymerase Chain Reaction Inhibitors for Cervical Cancer Screening Using Scraped Cells2017

    • Author(s)
      Yaku Hidenobu、Yoshida Yoshio、Okazawa Hidehiko、Kiyono Yasushi、Fujita Yuko、Miyoshi Daisuke
    • Journal Title

      Analytical Chemistry

      Volume: 89 Issue: 13 Pages: 6948-6953

    • DOI

      10.1021/acs.analchem.6b04777

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selective and robust stabilization of triplex DNA structures using cationic comb-type copolymer2017

    • Author(s)
      A. Yamayoshi, D. Miyoshi, Y. Zouzumi, Y. Matsuyama, J. Ariyoshi, N. Shimada, A. Murakami, T. Wada, A. Maruyama
    • Journal Title

      J. Phys. Chem., B

      Volume: 1221 Issue: 16 Pages: 4015-4022

    • DOI

      10.1021/acs.jpcb.7b01926

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] DNA G-wire formation using an artificial peptide is controlled by protease activity2017

    • Author(s)
      Usui, K., Okada, A., Sakashita, S., Shimooka, M., Tsuruoka, T., Nakano, S., Miyoshi, D., Mashima, T., Katahira, M., Hamada, Y.
    • Journal Title

      Molecules

      Volume: 22 Issue: 11 Pages: 1991-1991

    • DOI

      10.3390/molecules22111991

    • NAID

      120006501324

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 細胞環境化学模倣実験系におけるDNAの構造とその熱力学的安定性2017

    • Author(s)
      三好大輔
    • Journal Title

      日本核酸化学会誌

      Volume: 1 Pages: 13-19

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cell and Molecular Mechanics in Health and Disease2017

    • Author(s)
      Kawauchi K, Fujita H, Miyoshi D, Yim EK, Hirata H.
    • Journal Title

      BioMed Research International

      Volume: 2017 Pages: 2860241-2860241

    • DOI

      10.1155/2017/2860241

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A reversible B-A transition of DNA duplexes induced by synthetic cationic copolymers†2016

    • Author(s)
      Nonoka Yamaguchi, Yu-ki Zouzumi, Naohiko Shimada, Shu-ichi Nakano, Naoki Sugimoto, Atsushi Maruyama and Daisuke Miyoshi
    • Journal Title

      Chem. Commun.,

      Volume: 52 Issue: 47 Pages: 7446-7449

    • DOI

      10.1039/c6cc02237e

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Effects of trimethylamine N-oxide and urea on DNA duplex and G-quadruplex2016

    • Author(s)
      Yu-mi Ueda, Yu-ki Zouzumi, Atsushi Maruyama, Shu-ichi Nakano, Naoki Sugimoto, Daisuke Miyoshi
    • Journal Title

      Science and Technology of Advanced Materials

      Volume: 17 Issue: 1 Pages: 753-759

    • DOI

      10.1080/14686996.2016.1243000

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] DNA and RNA G-quadruplexes: structure, function, and ligand under cell-mimicking molecular crowding conditions2018

    • Author(s)
      Daisuke Miyoshi
    • Organizer
      International Conference on Current Trends in Materials Science and Engineering (CTMSE 2018)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] DNA and RNA G-quadruplexes under molecular crowding conditions2018

    • Author(s)
      Daisuke Miyoshi
    • Organizer
      IGIB seminar, Institute of Genomics & Integrative Biology, Delhi, India
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] What is the canonical structure of nucleic acids in cells?2018

    • Author(s)
      Daisuke Miyoshi
    • Organizer
      Institute Seminar, National Institute of Technology, Nagaland, Nagaland, India
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 脱ワトソン・クリックの核酸化学 (44): DNAの構造安定性に及ぼすヒストン模倣高分子と分子クラウディング環境の複合効果2018

    • Author(s)
      造住有輝, 宮田貴史, 嶋田直彦, 杉本直己, 丸山厚, 三好大輔
    • Organizer
      日本化学会第98回春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脱ワトソン・クリックの核酸化学 (45): ZnAPCによるグアニン四重らせん構造の選択的蛍光検出2018

    • Author(s)
      今川佳樹, 杉本直己, 三好大輔
    • Organizer
      日本化学会第98回春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脱ワトソン・クリックの核酸化学 (46): Thioflavin Tを用いたDNA i-motifの配列特異的検出2018

    • Author(s)
      小畠一起, 赤山詩織, 杉本直己, 三好大輔
    • Organizer
      日本化学会第98回春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脱ワトソン・クリックの核酸化学 (47): RNA四重らせん構造リガンドを用いた分子標的型光線力学療法の構築2018

    • Author(s)
      高木一樹, 安井貴俊, 伊藤功彦, 杉本渉, 川内敬子, 杉本直己, 三好大輔
    • Organizer
      日本化学会第98回春季年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脱ワトソン・クリックの核酸化学 (34): ヒトテロメアDNAを標的としたリガンドスクリー2017

    • Author(s)
      今川 佳樹, 小畠 一起, 寺田 康介, 前田 龍一,杉本 直己, 三好 大輔
    • Organizer
      日本化学会第97回春季年会
    • Place of Presentation
      慶応義塾大学日吉キャンパス(神奈川県横浜市)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 脱ワトソン・クリックの核酸化学 (33): mRNAの形成する四重らせん構造を標的とした亜鉛フタロシアニンによる光切断2017

    • Author(s)
      村田 耕平, 杉本 渉, 高木 一樹, 杉本 直己, 川内 敬子, 三好 大輔
    • Organizer
      日本化学会第97回春季年会
    • Place of Presentation
      慶応義塾大学日吉キャンパス(神奈川県横浜市)
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 核酸の高次構造を標的とした新しい機能性分子の開発2017

    • Author(s)
      三好大輔
    • Organizer
      メディカル ジャパン2017 大阪
    • Place of Presentation
      インテックス大阪(大阪府大阪市)
    • Year and Date
      2017-02-21
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] A new photodynamic therapy targeting mRNA G42017

    • Author(s)
      Daisuke Miyoshia, Kohei Murata, Wataru Sugimoto, Kazuki Takagi, Naoki Sugimoto, Keiko Kawauchi
    • Organizer
      6th International Meeting on Quadruplex Nucleic Acids
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 核酸四重らせん構造に選択的に結合する化合物のスクリーニング2017

    • Author(s)
      今川佳樹、小畠一起、寺田康介、杉本直己、三好大輔
    • Organizer
      日本ケミカルバイオロジー学会 第12回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 細胞核模倣環境におけるDNAの構造と熱力学的安定性2017

    • Author(s)
      造住 有輝、宮田 貴史、山口野乃花、嶋田 直彦、丸山  厚、三好 大輔
    • Organizer
      日本核酸医薬学会第3回年会,
    • Related Report
      2017 Annual Research Report
  • [Presentation] 核酸の高次構造を標的にする機能性分子の医療展開2017

    • Author(s)
      三好大輔
    • Organizer
      神戸医療産業都市クラスター交流会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 細胞の分子クラウディング環境における核酸の四重らせん構造とそれを標的にした機能性分子の開発2017

    • Author(s)
      三好大輔
    • Organizer
      49th Seminer, Japanese Association of Scientists in Singapore
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞夾雑模倣系の構築と細胞内活性分子設計指針の構築2017

    • Author(s)
      三好 大輔、杉本 直己
    • Organizer
      分子夾雑の生命化学 第一回公開シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] ヒストン模倣高分子のエピジェネティック修飾によるDNA との結合親和性への影響2017

    • Author(s)
      造住 有輝・山口 野乃花・嶋田 直彦・杉本 直己・丸山 厚・三好 大輔
    • Organizer
      第11回バイオ関連化学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] ハイスループット解析による核酸と生体低分子の相互作用評価2017

    • Author(s)
      田辺 和也・三好 大輔・杉本 直己・中野 修一
    • Organizer
      第11回バイオ関連化学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] グアニン四重らせん構造選択的化合物のスクリーニングおよび機能解析2017

    • Author(s)
      今川 佳樹・小畠 一起・寺田 康介・前田 龍一・中野 修一・杉本 直己・三好 大輔
    • Organizer
      第11回バイオ関連化学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] DNA and RNA G-quadruplexes: Structure, Stability, Function, and Ligand under Cell-mimicking Molecular Crowding Conditions.2017

    • Author(s)
      Daisuke Miyoshi1, Yu-ki Zouzumi, Yoshiki Imagawa, Wataru Sugimoto, Takatoshi Yasui, and Keiko Kawauchi
    • Organizer
      A3 Foresight 9th Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cell nucleus-mimicking system with synthetic cationic polymers2017

    • Author(s)
      Daisuke Miyoshi
    • Organizer
      1st Minisymposium on Material Biology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Evaluation of interactions between DNA G-quadrplex and small biomolecules selected by high-throuput screenin2017

    • Author(s)
      K.Tanabe, D.Miyoshi, N.Sugimoto, S.Nakano
    • Organizer
      第44回国際核酸化学シンポジウム
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of DNA structure and stability by combined effects of histone-mimicking polymers and osmolytes2017

    • Author(s)
      Y.Zouzumi, N.Yamaguchi, N.Shimada, N.Sugimoto, A.Maruyama, D.Miyoshi
    • Organizer
      第44回国際核酸化学シンポジウム
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of cell nucleus mimicking system based on molecular crowding effects on DNA structures2017

    • Author(s)
      Yu-ki Zouzumi, Takafumi Miyata, Naohiko Shimada, Atushi Maruyama, Naoki Sugimoto, Daisuke Miyoshi
    • Organizer
      2nd International Symposium on Biofunctional Chemistry (ISBC2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細胞の分子クラウディング環境が制御する核酸の構造多様性2017

    • Author(s)
      三好大輔
    • Organizer
      ナノメディシンセミナー2017
    • Place of Presentation
      甲南大学ポートアイランドキャンパス(兵庫県神戸市)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 細胞核内の化学的模倣環境におけるDNA構造の熱安定性2017

    • Author(s)
      造住有輝、山口野乃花、嶋田直彦、丸山厚、三好大輔
    • Organizer
      ナノメディシンセミナー2017
    • Place of Presentation
      甲南大学ポートアイランドキャンパス(兵庫県神戸市)
    • Related Report
      2016 Research-status Report
  • [Presentation] アニオン性亜鉛フタロシアニンを用いたRNA四重らせん構造標的型光増感剤の開発2017

    • Author(s)
      村田耕平、杉本渉、川内敬子、三好大輔
    • Organizer
      ナノメディシンセミナー2017
    • Place of Presentation
      甲南大学ポートアイランドキャンパス(兵庫県神戸市)
    • Related Report
      2016 Research-status Report
  • [Presentation] Pseudo-cellular environmental systems for design of functional molecules2016

    • Author(s)
      D. Miyoshi
    • Organizer
      10th Anniversary International Symposium on Nanomedicine (ISNM2016)
    • Place of Presentation
      Audiotorium at National Institute of Advanced Industrial Science and Technology (AIST) (茨城県つくば市)
    • Year and Date
      2016-11-24
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Stabilization of A-form nucleic acid by synthetic cationic copolymers2016

    • Author(s)
      Yu-ki Zouzumi, Nonoka Yamaguchi, Naohiko Shimada, Shu-ichi Nakano, Naoki Sugimoto, Atsushi Maruyama, Daisuke Miyoshi
    • Organizer
      The 43rd International Symposium on Nucleic Acids
    • Place of Presentation
      100th Anniversary Hall, Kumamoto University(熊本県熊本市)
    • Year and Date
      2016-09-27
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effects of epigenetic modifications of histone tails on transcriptional2016

    • Author(s)
      Kohei Murata, Shu Higashida, Smritimoy Pramanik, Naoki Sugimoto, Daisuke Miyoshi
    • Organizer
      The 43rd International Symposium on Nucleic Acids
    • Place of Presentation
      100th Anniversary Hall, Kumamoto University(熊本県熊本市)
    • Year and Date
      2016-09-27
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 亜鉛フタロシアニンによるがん関連mRNAの光切断2016

    • Author(s)
      村田耕平、杉本渉、高木一樹、松野仁志、杉本直己、川内敬子、三好大輔
    • Organizer
      第10回バイオ関連化学シンポジウム
    • Place of Presentation
      石川県立音楽堂(石川県金沢市)
    • Year and Date
      2016-09-10
    • Related Report
      2016 Research-status Report
  • [Presentation] グラフェン酸化物-DNAバイオセンサーの検出感度に対するDNA構造の効果2016

    • Author(s)
      造住有輝、坂下祐介、上田侑美、杉本直己、三好大輔
    • Organizer
      第10回バイオ関連化学シンポジウム
    • Place of Presentation
      石川県立音楽堂(石川県金沢市)
    • Year and Date
      2016-09-10
    • Related Report
      2016 Research-status Report
  • [Presentation] DNA structure and thermodynamics under molecular crowding conditions with histone2016

    • Author(s)
      Daisuke Miyoshi, Nonoka Yamaguchi, Yu-mi Ueda, Yu-ki Zouzumi,
    • Organizer
      The 22th International Round Table on Nucleosides, Nucleotides and Nucleic Acids (XXII IRT)
    • Place of Presentation
      Institut Pasteur, Paris (France)
    • Year and Date
      2016-07-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] mRNA が形成する四重らせん構造を狙った分子標的型光線力学療2016

    • Author(s)
      村田耕平、松野仁志、杉本渉、川内敬子、杉本直己、三好大輔
    • Organizer
      日本ケミカルバイオロジー学会 第11回年会
    • Place of Presentation
      京都テルサ テルサホール(京都府京都市)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 細胞の分子クラウディングによって誘起される核酸の構造多様性2016

    • Author(s)
      三好大輔
    • Organizer
      先端ケミカルバイオロジー研究会
    • Place of Presentation
      京都大学物質ー細胞統合システム拠点(京都府京都市)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 細胞内分子クラウディング環境で安定化するDNAの非標準構造2016

    • Author(s)
      三好大輔
    • Organizer
      同志社大学生命医科学部セミナー
    • Place of Presentation
      同志社大学京田辺キャンパス医心館(京都府京田辺市)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Book] Chapter 6. Assays for Telomerase Activity toward Applications of Cancer Diagnosis in GQuadruplex2016

    • Author(s)
      Hidenobu Yaku, Daisuke Miyoshi
    • Total Pages
      210
    • Publisher
      Nova Science Publishers
    • Related Report
      2016 Research-status Report
  • [Remarks] 甲南大学分子設計化学研究室(三好研究室)

    • URL

      http://www.pi.konan-u.ac.jp/miyoshi/

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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